General interest items edited by Janice Flahiff

New research finds that misdiagnoses lead to increased risk of incorrect antibiotic use, threatening patient outcomes and antimicrobial efficacy, while increasing healthcare costs. The study was published online today in Infection Control & Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America.

“Antibiotic therapies are used for approximately 56 percent of inpatients in U.S. hospitals, but are found to be inappropriate in nearly half of these cases, and many of these failures are connected with inaccurate diagnoses,” said Greg Filice, MD, lead author of the study. “The findings suggest that antimicrobial stewardship programs could be more impactful if they were designed to help providers make accurate initial diagnoses and to know when antibiotics can be safely withheld.”

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Additionally, researchers found that overall, only 58 percent of patients received a correct diagnosis, indicating that diagnostic errors were more prevalent in this study than in previous studies unrelated to antimicrobial use. The most common incorrect diagnoses identified by researchers were pneumonia, cystitis, urinary tract infections, kidney infections and urosepsis.

Contributing factors which the researchers said may lead to inaccurate diagnosis and inappropriate antibiotic use include:

Healthcare workers (HCWs) relying on intuitive processes, instead of analytical processes which are more reliable, safe and effective.

Bacteria that cause many hospital-associated infections are ready to quickly share genes that allow them to resist powerful antibiotics. The illustration, based on electron micrographs and created by the Centers for Disease Control and Prevention, shows one of these antibiotic-resistant bacteria. Credit: CDC/James Archer

Antibiotic resistance is poised to spread globally among bacteria frequently implicated in respiratory and urinary infections in hospital settings, according to new research at Washington University School of Medicine in St. Louis.

The study shows that two genes that confer resistance against a particularly strong class of antibiotics can be shared easily among a family of bacteria responsible for a significant portion of hospital-associated infections.

Drug-resistant germs in the same family of bacteria recently infected several patients at two Los Angeles hospitals. The infections have been linked to medical scopes believed to have been contaminated with bacteria that can resist carbapenems, potent antibiotics that are supposed to be used only in gravely ill patients or those infected by resistant bacteria.

“Carbapenems are one of our last resorts for treating bacterial infections, what we use when nothing else works,” said senior author Gautam Dantas, PhD, associate professor of pathology and immunology. “Given what we know now, I don’t think it’s overstating the case to say that for certain types of infections, we may be looking at the start of the post-antibiotic era, a time when most of the antibiotics we rely on to treat bacterial infections are no longer effective.”

Researchers at Oregon State University have discovered that antibiotics have an impact on the microorganisms that live in an animal’s gut that’s more broad and complex than previously known.

The findings help to better explain some of the damage these medications can do, and set the stage for new ways to study and offset those impacts.

The work was published online in the journal Gut, in research supported by Oregon State University, the Medical Research Foundation of Oregon and the National Institutes of Health.

Researchers have known for some time that antibiotics can have unwanted side effects, especially in disrupting the natural and beneficial microbiota of the gastrointestinal system. But the new study helps explain in much more detail why that is happening, and also suggests that powerful, long-term antibiotic use can have even more far-reaching effects.

Scientists now suspect that antibiotic use, and especially overuse, can have unwanted effects on everything from the immune system to glucose metabolism, food absorption, obesity, stress and behavior.

The issues are rising in importance, since 40 percent of all adults and 70 percent of all children take one or more antibiotics every year, not to mention their use in billions of food animals. Although when used properly antibiotics can help treat life-threatening bacterial infections, more than 10 percent of people who receive the medications can suffer from adverse side effects.

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“Prior to this most people thought antibiotics only depleted microbiota and diminished several important immune functions that take place in the gut,” Morgun said. “Actually that’s only about one-third of the picture. They also kill intestinal epithelium. Destruction of the intestinal epithelium is important because this is the site of nutrient absorption, part of our immune system and it has other biological functions that play a role in human health.”

The research also found that antibiotics and antibiotic-resistant microbes caused significant changes in mitochondrial function, which in turn can lead to more epithelial cell death. That antibiotics have special impacts on the mitochondria of cells is both important and interesting, said Morgun, who was a co-leader of this study with Dr. Natalia Shulzhenko, a researcher in the OSU College of Veterinary Medicine who has an M.D. from Kharkiv Medical University.

Mitochondria plays a major role in cell signaling, growth and energy production, and for good health they need to function properly.

But the relationship of antibiotics to mitochondria may go back a long way. In evolution, mitochondria descended from bacteria, which were some of the earliest life forms, and different bacteria competed with each other for survival. That an antibiotic would still selectively attack the portion of a cell that most closely resembles bacteria may be a throwback to that ingrained sense of competition and the very evolution of life.

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Digestive dysfunction is near the top of the list, with antibiotic use linked to such issues as diarrhea and ulcerative colitis. But new research is also finding links to obesity, food absorption, depression, immune function, sepsis, allergies and asthma.

This research also developed a new bioinformatics approach named “transkingdom network interrogation” to studying microbiota, which could help further speed the study of any alterations of host microbiota interactions and antibiotic impact. This could aid the search for new probiotics to help offset antibiotic effects, and conceivably lead to systems that would diagnose a person’s microbiome, identify deficiencies and then address them in a precise and individual way.

A way to eradicate cancer stem cells, using the side-effects of commonly used antibiotics, has been discovered by a University of Manchester researcher following a conversation with his young daughter.

His new paper, published in Oncotarget, opens up the possibility of a treatment for cancer, which is highly effective and repurposes drugs which have been safely used for decades.

Mitochondria are the ‘engine’ parts of the cells and are the source of energy for the stem cells as they mutate and divide to cause tumours. Cancer stem cells are strongly associated with the growth and recurrence of all cancers and are especially difficult to eradicate with normal treatment, which also leads to tumours developing resistance to other types of therapy.

Professor Lisanti said: “I was having a conversation with Camilla about how to cure cancer and she asked why don’t we just use antibiotics like we do for other illnesses. I knew that antibiotics can affect mitochondria and I’ve been doing a lot of work recently on how important they are to the growth of tumours, but this conversation helped me to make a direct link.”

Professor Lisanti worked with colleagues from The Albert Einstein College of Medicine, New York and the Kimmel Cancer Centre, Philadelphia. The team used five types of antibiotics – including one used to treat acne (doxycycline) – on cell lines of eight different types of tumour and found that four of them eradicated the cancer stem cells in every test. This included glioblastoma, the most aggressive of brain tumours, as well as lung, prostate, ovarian, breast, pancreatic and skin cancer.

Mitochondria are believed to be descended from bacteria which joined with cells early on in the evolution of life. This is why some of the antibiotics which are used to destroy bacteria also affect mitochondria, though not to an extent which is dangerous to people. When they are present in stem cells, mitochondria provide energy for growth and, crucially, for division, and it is this process going wrong which leads to cancer.

In the lab, the antibiotics had no harmful effect on normal cells, and since they are already approved for use in humans, trials of new treatments should be simpler than with new drugs – saving time and money.

Professor Lisanti said: “This research makes a strong case for opening new trials in humans for using antibiotics to fight cancer. Many of the drugs we used were extremely effective, there was little or no damage to normal cells and these antibiotics have been in use for decades and are already approved by the FDA for use in humans. However, of course, further studies are needed to validate their efficacy, especially in combination with more conventional therapies.”

Dr Matthew Lam, Senior Research Officer at Breakthrough Breast Cancer, said: “The conclusions that the researchers have drawn, whilst just hypotheses at this stage, are certainly interesting. Antibiotics are cheap and readily available and if in time the link between their use and the eradication of cancer stem cells can be proved, this work may be the first step towards a new avenue for cancer treatment.

“This is a perfect example of why it is so important to continue to invest in scientific research. Sometimes there are answers to some of the biggest questions right in front of us but without ongoing commitment to the search for these answers, we’d never find them.”

Importantly, previous clinical trials with antibiotics – intended to treat cancer-associated infections, but not cancer cells – have already shown positive therapeutic effects in cancer patients. These trials were performed on advanced or treatment-resistant patients.

In the lung cancer patients, azithromycin, the antibiotic used, increased one-year patient survival from 45% to 75%. Even lymphoma patients who were ‘bacteria-free’ benefited from a three-week course of doxycycline therapy, and showed complete remission of the disease. These results suggest that the antibiotic’s therapeutic effects were actually infection-independent.

“As these drugs are considerably cheaper than current therapies, they can improve treatment in the developing world where the number of deaths from cancer is predicted to increase significantly over the next ten years,” said Dr Federica Sotgia, another leader of the study.

US scientists are asking the public to join them in their quest to mine the Earth’s soil for compounds that could be turned into vital new drugs.

Spurred on by the recent discovery of a potential new antibiotic in soil, the Rockefeller University team want to check dirt from every country in the world.

They have already begun analysing samples from beaches, forests and deserts across five continents.

But they need help getting samples.

Which is where we all come in.

Citizen science

On their Drugs From Dirt website, they say: “The world is a big place and we can’t get get to all of the various corners of it.

“We would like some assistance in sampling soil from around the world. If this sounds interesting to you – sign up.”

They want to hear from people from all countries and are particularly keen to receive samples from unique, unexplored environments such as caves, islands, and hot springs.

Such places, they say, could house the holy grail – compounds produced by soil bacteria that are entirely new to science.

Researcher Dr Sean Brady told the BBC: “We are not after hundreds of thousands of samples. What we really want is a couple of thousand from some really unique places that could contain some really interesting stuff. So it’s not really your garden soil we are after, although that will have plenty of bacteria in it too.”

He said they would also be interested to hear from schools and colleges that might want to get involved in the project.

From the 185 samples they have tested so far there are some promising results, the researchers say in the journal eLife.

Biosynthetic dark matter

Dr Brady and colleagues have found compounds that might yield better derivatives of existing drugs.

In a hot spring sample from New Mexico, they found compounds similar to those that produce epoxamicin – a natural molecule used as the starting point for a number of cancer drugs.

In samples from Brazil, they found genes that might offer up new versions of another important cancer drug called bleomycin.

And in soils from the American southwest, they hope to find compounds similar to the drug rifamycin that could help with treatment-resistant tuberculosis.

Researchers at Oregon State University and other institutions today announced the successful use of a new type of antibacterial agent called a PPMO, which appears to function as well or better than an antibiotic, but may be more precise and also solve problems with antibiotic resistance.

A new study by researchers at the Stanford University School of Medicine could help pinpoint ways to counter the effects of the antibiotics-driven depletion of friendly, gut-dwelling bacteria.

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“Antibiotics open the door for these pathogens to take hold. But how, exactly, that occurs hasn’t been well understood,” Sonnenburg said.

In the first 24 hours after administration of oral antibiotics, a spike in carbohydrate availability takes place in the gut, the study says. This transient nutrient surplus, combined with the reduction of friendly gut-dwelling bacteria due to antibiotics, permits at least two potentially deadly pathogens to get a toehold in that otherwise more forbidding environment.

In the past decade or so, much has been learned about the complex microbial ecosystem that resides in every healthy mammal’s large intestine, including ours. The thousands of distinct bacterial strains that normally inhabit this challenging but nutrient-rich niche have adapted to it so well that we have difficulty living without them. They manufacture vitamins, provide critical training to our immune systems and even guide the development of our own tissues. Antibiotics decimate this gut-microbe ecosystem, which begins bouncing back within a few days but may take a month or more to regain its former numbers. And the ecosystem appears to suffer the permanent loss of some of its constituent bacterial strains.

It is thought that our commensal, or friendly, bacteria serve as a kind of lawn that, in commandeering the rich fertilizer that courses through our gut, outcompetes the less-well-behaved pathogenic “weeds.” It has also been suggested that our commensal bugs secrete pathogen-killing factors. Another theory holds that the disruption of our inner microbial ecosystem somehow impairs our immune responsiveness.

Could pave way for development of enhanced delivery and storage in third world, save billions in cost

Researchers funded by the National Institutes of Health have developed a new silk-based stabilizer that, in the laboratory, kept some vaccines and antibiotics stable up to temperatures of 140 degrees Fahrenheit. This provides a new avenue toward eliminating the need to keep some vaccines and antibiotics refrigerated, which could save billions of dollars every year and increase accessibility to third world populations.

Vaccines and antibiotics often need to be refrigerated to prevent alteration of their chemical structures; such alteration can result in less potent or ineffective medications. By immobilizing their bioactive molecules using silk protein matrices, researchers were able to protect and stabilize both live vaccines and antibiotics when stored at higher than recommended temperatures for periods far longer than recommended….

Show up at the emergency room or your doctor’s office with symptoms of a serious infection, and there’s a good chance you’ll get an antibiotic. You might even get a few.

But antibiotics don’t work on viruses. And a particular antibiotic may be suited for one kind of germ, but not another.

The problem for your doctor — and you — is that it can take days to grow enough of the germs afflicting you to identify them conclusively using traditional tests. And if you’re really sick, the doctor may try a bunch of antibiotics right away, just to be sure one of them starts getting you back on the road to health….

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Faster, more specific tests would help. And the Food and Drug Administration has recently approved some. This week, while you might have been distracted by the Supreme Court, the agency cleared a test for a dozen bacteria that cause infections in the blood.

“Bloodstream infections are always treated with antimicrobial drugs, and it is essential to identify which antimicrobial drug is appropriate for a specific patient as quickly as possible,” FDA’s Alberto Gutierrez said in a statement. “This new test is an important tool that will help physicians treat patients quickly with the correct antibiotics.”

The test, made by Nanosphere, works in a few hours instead of days. It fingerprints the germs’ DNA and can even detect when the bugs carry genes that render them resistant to some antibiotics. The test costs less than $100….

New treatments that combat the growing problem of antibiotic resistance by disarming rather than killing bacteria may be on the horizon, according to a new study.

Published in Nature Structure and Molecular Biology, research led by Monash Universityshowed a protein complex called the Translocation and Assembly Module (TAM), formed a type of molecular pump in bacteria. The TAM allows bacteria to shuttle key disease-causing molecules from inside the bacterial cell where they are made, to the outside surface, priming the bacteria for infection.
Lead author and PhD student Joel Selkrig of the Department of Biochemistry and Molecular Biology at Monash said the work paves the way for future studies to design new drugs that inhibit this process.
“The TAM was discovered in many disease-causing bacteria, from micro-organisms that cause whooping cough and meningitis, to hospital-acquired bacteria that are developing resistance to current antibiotics,” Mr Selkrig said.
“It is a good antibacterial target because a drug designed to inhibit TAM function would unlikely kill bacteria, but simply deprive them of their molecular weaponry, and in doing so, disable the disease process.”
“By allowing bacteria to stay alive after antibiotic treatment, we believe we can also prevent the emergence of antibiotic resistance, which is fast becoming a major problem worldwide.”…

Drugs used to overcome cancer may also combat antibiotic resistance, finds a new study led by Gerry Wright, scientific director of the Michael G. DeGroote Institute for Infectious Disease Research at McMaster University. “Our study found that certain proteins, called kinases, that confer antibiotic resistance are structurally related to proteins important in cancer,” says Wright about the study published in Chemistry & Biology…

Results
The rate of MRSA was 4.5 per 100 000 per year. Of 297 cases and 9357 controls, 52.5% and 13.6%, respectively, received antibacterial drug prescriptions during the 150-day exposure window. The adjusted RR with any antibacterial drug was 3.5 (95% confidence interval [CI], 2.6-4.8). The RRs increased with the number of prescriptions (2.2 [95% CI, 1.5-3.2], 3.3 [95% CI, 1.9-5.6], 11.0 [95% CI, 5.6-21.6], and 18.2 [95% CI, 9.4-35.4] for 1, 2, 3, and 4 prescriptions, respectively). The RR was particularly elevated for quinolones at 14.8 (95% CI, 3.9-55.8), with wide variation among antibacterial classes.

Conclusion
While close to half of children were diagnosed as having MRSA in the community without prior antibacterial drugs, such agents are associated with a dose-dependent increased risk, concordant with findings in adults.

According to the World Health Organization, antibiotic-resistant bacteria are one of the top three threats to human health. Patients in hospitals are especially at risk, with almost 100,000 deaths due to infection every year in the U.S. alone.

Now Dr. Udi Qimron of the Department of Clinical Microbiology and Immunology at Tel Aviv University’s Sackler Faculty of Medicine has developed an efficient and cost-effective liquid solution that can help fight antibiotic-resistant bacteria and keep more patients safe from life-threatening infections. The solution is based on specially designed bacteriophages — viruses that infect bacteria — that can alter the genetic make-up of antibiotic-resistant bacteria. “We have genetically engineered the bacteriophages so that once they infect the bacteria, they transfer a dominant gene that confers renewed sensitivity to certain antibiotics,” explains Dr. Qimron.

The solution, recently detailed in the journal Applied and Environmental Microbiology, could be added to common antibacterial cleansers used on hospital surfaces, turning resistant bacteria into sensitive bacteria. It’s easy to prepare, easy to apply, and non-toxic, Dr. Qimron notes. He estimates that one liter of the growth medium — the liquid in which the bacteriophages are grown — will cost just a few dollars.

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Two steps to disarming bacteria

Added to cleansers, Tellurite represents the second step in a two-part process. A Tellurite compound, which is toxic to bacteria, would also be spread on all surfaces to wipe out the bacteria that had not been rendered sensitive, and thus the entire population of the surface bacteria would be sensitized. The combination is designed to first disarm, and then kill dangerous bacteria.

Next, the solution will be tested in pre-clinical animal trials to ensure its safety before being made available for wider use at hospitals…

The world is moving towards the unthinkable scenario of untreatable infections as fewer antibacterial drugs are discovered and more and more people are becoming resistant to existing drugs, researchers from University of Birmingham, England, reported in The Lancet Infectious Diseases. The article coincides with the European Antibiotics Awareness Day, and warns about the urgency of the situation and the actions needed to turn it around.

People have become so used to antibioticsbeing readily available that there is no sense of urgency regarding the lack of new drugs, or in existing antibiotic’s essential tasks to prolong life.

A wide spectrum of medical procedures, including many elderly people whose immune system has weakened, rely on antibiotics to fend off opportunistic infections. Even fairly simple procedures, for example, transrectal prostate biopsies that are typically used to detectprostate cancer, become problematic because of antibiotic resistant infections.

Author Professor Laura Piddock explains:

“When patients are denied treatment with a new cancer drug because of its expense, there is public outrage despite the possibility of extending life by only a few weeks. Antibiotics are not perceived as essential to health or the practice of medicine, despite such agents saving lives so that individuals can live for many years after infection.”

According to an announcement made by the WHO (World Health Organization) 2 years ago, antibiotic resistance is one of the three biggest health threats, yet politicians, the public, and the media have been slow to understand the urgency of the situation. …

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Put simply: The pharmaceutical industry finds that after spending a lot of money developing a new drug, they are then faced with many regulatory barriers, only to find that when their new medication is finally approved, it is not effective for long because the bacterium rapidly develops resistance to it.

One serious problem is the approach of drug trials for antibiotics. Researchers recruit people with infections who are not necessarily infected with the bacteria that the drug is designed to kill, which in turn affects efficacy results.

According to Professor Piddock, this problem could be eliminated by using point-of-care tests to identify the precise bacteria causing the infection and excluding that particular individual from the study if they do not have the bacterium which is being targeted. The number of people required for a trial is currently prohibitively high, yet an approach like this would reduce the number of people needed for each trial, and also ensure that those participating receive the drug that is specifically targeted to their infection.

The profile of this issue must be raised in order to overcome the barriers to new antibiotic discovery and development. In response to this, the British Society of Antimicrobial Chemotherapy has launched Antibiotic Action, a campaign that has already obtained worldwide support, from the Infectious Diseases Society of America, ReACT, charities, and not-for-profit agencies amongst others.

All these initiatives represent patients who depend on effective antibiotic treatment.

Professor Piddock states:

“As absence of new antibiotics affects everyone, shifting this issue out of the medical arena and into the public eye is paramount, which will stimulate governments to act. To do this, Antibiotic Action is using the latest communication methods including Twitter; this approach will assist as many individuals as possible to sign one of two on-line petitions, one for UK citizens and another for those from outside the UK.” (http://antibiotic-action.com/petition/ )

ScienceDaily (Apr. 8, 2011) — Doctors at the Veterans Affairs Boston Healthcare System are testing a new kind of clinical trial that’s not only less costly but guides doctors to switch to the best treatment even before the trial is completed. The new approach — called a point-of-care clinical trial — was developed by Stanford University biostatistician Philip Lavori, PhD, and a Boston-based team as an alternative to expensive, lengthy, double-blind, placebo-controlled clinical trials to compare drugs and procedures that are already in regular use.

“The goal of point-of-care clinical trials is to deliver the best care to patients while learning from each experience and redefining that care,” said Lavori, a professor of health research and policy at Stanford’s School of Medicine and the senior author of an article on the method to be published online April 4 in Clinical Trials. “This ‘learning and improving’ loop will enable health-care institutions to more rapidly fold improvements into their medical practices,” he said….

…”The idea of embedding research into clinical care has been around for quite awhile but to my knowledge this is the first time that a randomized trial has been fully integrated into a hospital’s informatics system,” said Fiore. “It demonstrates an effective way to use electronic medical records to improve health care at a local level.”…

Antibiotic overuse and resistance have emerged as major threats during the past two decades. Following an outbreak of Clostridium difficile infections, which often result from antibiotic use, health care professionals in Quebec, Canada targeted physicians and pharmacists with an education campaign that reduced outpatient antibiotic use, according to a study published in Clinical Infectious Diseases and now available online.

The Quebec Minister of Health and the Quebec Medication Council collaborated with designated physicians and pharmacists to develop guidelines to improve prescribing practices. First issued in January 2005, the guidelines emphasized proper antibiotic use, including not prescribing antibiotics when viral infections were suspected and selecting the shortest possible duration of treatment. Approximately 30,000 printed copies of the original recommendations were distributed to all physicians and pharmacists in Quebec. An additional 193,500 copies were downloaded from the Medication Council’s website.

During the year after the guidelines were initially distributed, the number of outpatient antibiotic prescriptions in Quebec decreased 4.2 percent. In other Canadian provinces, the number of these prescriptions increased 6.5 percent during the same period.

According to study author Karl Weiss, MD, of the University of Montreal, “It is possible to decrease antibiotic consumption when physicians, pharmacists, state governments, etc., are working together for a common goal. This is the key to success: having everybody involved and speaking with a common voice.”

Dr. Weiss added, “Simple, short, easy-to-use guidelines have an impact on physicians when they are readily available. The web is an increasingly important tool to reach our audience and should now be used as such in the future. With handheld electronic devices available for all health care professionals, these downloadable guidelines can be accessed and used at any time and any circumstance.”

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About

This blog presents a sampling of health and medical news and resources for all. Selected articles and resources will hopefully be of general interest but will also encourage further reading through posted references and other links. Currently I am focusing on public health, basic and applied research and very broadly on disease and healthy lifestyle topics.

Several times a month I will post items on international and global health issues. My Peace Corps Liberia experience (1980-81) has formed me as a global citizen in many ways and has challenged me to think of health and other topics in a more holistic manner. (For those wishing to see pictures of a 2009 Friends of Liberia service trip to this West African country, please visit www.fol.org. My photo album is included).

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